Basic Pharmacology and Pharmacodynamics

University:
Franklin University
Course:
BIO-201 | Introductory Biology I
Academic year:

2021
Views:

132

Pages:

59
Author:

LunarLuminary

Basic Pharmacology and Pharmacodynamics Drug  Drug is any substance or product that is used or is intended to be used to modify physiological systems or pathological states for the benefit of the recipient. Drug Names     Chemical- states its chemical composition and molecular structure Generic- usually suggested by the manufacturer Official- as listed in the pharmacopeia (BP, USP,…) Brand- The trade or proprietary name. Drug Names    example Chemical name: 1,4 benzodiazepine analog Generic name: Alprazolam Official name: Alprazolam, USP Brand name: Alprax® The nature & sources of drugs       Minerals- MgSo4, liquid paraffin Animals- Insulin, Thyroid hormones Plants- Morphine, quinine Synthetic- Aspirin, sulfonamides Microorganisms- penicillin, other antibiotics Genetic engineering- human insulin, human GH Pharmacology  The study of the interactions that occur between a living organism and drugs and/or chemicals that affect normal or abnormal biochemical functions and produces a biologic response. Pharmacokinetics Pharmacodynamics Pharmacology   Pharmacodynamics What the drug does to the body Pharmacokinetics What the body does to the drug ADME Pharmacokinetics Gives information about:     Absorption Distribution Metabolism Elimination Which are necessary for drug therapy of patients Pharmacokinetics     Absorption How the drug is moved into blood stream from the site of administration? Distribution How much drug is moved to various body tissues/organs dependes on blood flow through tissues. Metabolism How the drug is altered-broken down? Excretion How much of the drug is removed from the body? Pharmacodynamics    It covers all the aspects of “what a drug does to the body” It is the study of the mechanism by which the drug produces a response in the body. How a drug act in the body. Drug Action    How and where the effect is produced called the action. Action: the cellular processes involved in the drug and cell interaction Effect:   The type of response produced by drug. The physiologic reaction of the body to the drug. The fate of Drug in the body (4) Binds (2) Absorbed (6) Excreted (3) Distributed (1) Administered (5) Inactivated Drugs mechanism of action  Only a handful of drugs act by virtue of their simple physical or chemical property. Examples are: Drug actions  many drugs inhibit enzymes • Enzymes control a number of metabolic processes • A very common mode of action of many drugs  in the patient (ACE inhibitors)  in microbes (sulfas, penicillins)  in cancer cells (5-FU, 6-MP)  some drugs bind to:  proteins (in patient, or microbes)  the genome (cyclophosphamide)  microtubules (vincristine) How drugs act? • Majority of drugs produce their effects by interacting with a discrete target biomolecule, which usually is a protein. • This confers selectivity of action to the drug. • Functional proteins that are target of drug action are in four major categories: • • • • Enzymes- cyclooxygenase, Ach estrase Ion channels- voltage gated Na+, K+, Ca++ Transporters- Na+/K+ pump, proton pump Receptors- Ach receptors, epinephrine receptors Receptors • Specific macromolecular components of the cell which when binds with ligand produces positive or negative biological response • Situated on the surface/inside the cell. Receptors      Receptors are macromolecules Most are proteins Present either on the cell surface, cytoplasm or in the nucleus Drug should reach to its receptor, to be able to produce response (determined by drug pharmacokinetics) Drugs bind to receptor and produce biologic effect (pharmacodynamics) G proteins Cytoplasmic receptors Drug-receptor interaction D + R = DR > pharmacological effect   The DR interaction is through weak chemical bonds such as ionic or hydrogen bonds The drug binds and dissociate repeatedly (a dynamic effect) Only a domain on drug molecule binds to the receptor hydromorphone morphine codeine Drug-Receptor complex Drug+Receptor‒‒› D-R complex ‒‒› Effect (response)    The response depends on the number of receptors occupied by the drug molecules. The maximum response occurs when all receptors are occupied by the drug molecules. This interaction can be shown by D-R curve. Dose-response curve to explain some pharmacologic concepts Dose-response curves Dose-response curves Terminology    Affinity: inherent ability of the drug to bind with the receptor Efficacy (intrinsic activity): inherent ability of the drug to induce a physiological response Potency: an expression of the activity of the drug, in terms of the concentration or amount needed to produce a defined effect Terminology    Agonist: It activates a receptor to produce an effect similar to that of the physiological signal molecule. Antagonist: It prevents the action of an agonist on a receptor but does not have any effect of its own. Partial agonist: It activates a receptor to produce sub maximal effect but antagonizes the action of full agonist. 0-----------------------1 ‫پاسخ‬-‫مقایسه پوتنسی با استفاده ازمنحنی های دوز‬  Affinity  Potency % increase in pain threshold  Efficacy More potent Less potent 100 75 50 Hydromorphine Morphine Codeine Aspirin 25 1 10 100 Log dose (mg) 1.7 Maximum Effect   Drugs vary in their ability to produce an effect They may act by different mechanisms (at different receptors) They may have more or less efficacy at the same receptor Max. effect More 100 75 Less 50 Hydromorphine Morphine Codeine Aspirin 25 1 10 100 Log dose (mg) 1.7 Percent Effect Dose-effect curves 100 A B 75 50 Z C 25 1 10 100 Log dose (mg) Potency hydromorphone morphine codeine Potency Heroin (diacetylmorphine) fentanyl morphine 100 Potency  ED50 - Dose that produces an effect in 50% of a population LD50 - Dose that kills 50% (TD = toxic TI - Therapeutic Index (LD50 /ED50) Lethality 50 ED50 TD50 Low High Log drug dose 100 dose)  Desired effect Percent responding  Drug A Drug B 50 1.8 ED50 TD50 Low Log drug dose High Drug A 100 sleep death Percent 50 Responding 0 ED50 2004-2005 dose LD50 Drug B 100 Percent Responding sleep death 50 0 ED50 2004-2005 dose LD50 Agonists vs Antagonists  Agonist A drug that binds to receptor and has a cellular (pharmacological) effect  Antagonist A drug that binds to a receptor but produces no direct cellular effect Antagonists produce their effects by blocking the action of an agonist, or an endogenous ligand (e.g., a transmitter), at that receptor Receptor antagonism • The antagonist is chemically similar to the agonist, competes with it and binds to the same site to the exclusion of the agonist molecule. • Because the antagonist has affinity but no intrinsic activity, no response is produced. And the Log D-R curve of the agonist is shifted to the right. Competitive antagonism – Binds to the same receptor that agonist binds. – Antagonist shifts the D-R curve to the right. – Higher doses of agonist can overcome its effect. Competitive antagonism Naloxone Morphine Antagonist Agonist